There are many types of fluids that would benefit from interrogation systems that maintain the integrity of the fluid in the system. For example, to name one, it is understood that there complex interactions between phospholipids and membrane-associated proteins, such as those involved in Anti-Phospholipid Syndrome (APS) and a multitude of other human diseases. Yet most of the tools, methods, and approaches to interrogate these systems lack a similar level of sophistication. Some systems that better mimic in vivo membranes have been described but tend to have limited throughput. Current methods used to create micropatterned lipid arrays include microcontact printing, deep ultraviolet photolithography (UV), the use of prepatterned substrates, and 2D microfluidics. Microcontact printing utilizes a stamp to transfer material onto a substrate. Deep-UV radiation uses a photomask to protect the array regions while the exposed regions are degraded through exposure to UV radiation. Hand or robotic pipetting can be used with prepatterned substrates to corral the material into spatially distinct regions.
Many of these methods employ backfilling with vesicles to create multicomposition arrays, limiting the number of bilayers with distinct compositions. Robotics can generate multicomponent membrane arrays with small spot sizes (250 μm), but due to the small volumes (picoliters), this is typically performed in a humidity chamber (˜98% humidity) to prevent evaporation. The use of 2D microfluidics for the creation of lipid arrays involves introducing a solution of vesicles through a single plane of microchannels, producing parallel lanes of patterned lipids. This offers a simple and low-cost alternative, but the 2D flow lanes limit the ability to create high density arrays. An approach that combines both the sophistication of a fluid membrane bilayer and the robustness and throughput of solid-supported arrays is sorely needed for certain types of diagnostics, such as APS diagnostic testing.
More generally, all major human diseases including metabolic autoimmune diseases, vascular diseases, neurological diseases, and cancer have essential pathologic mechanisms involving dysfunctional cell and/or internal membranes. The combination of fluid lipid bilayers and membrane proteins constitute the major structural components of biological cell membranes. It would therefore be desirable to generate arrayed biomembrane bilayers consisting of both lipid and protein supported by a solid surface while maintaining their three-dimensional properties. This would enable analysis of important integral membrane and lipid-associated proteins in a more native-like environment, which is an environment that is needed for proper biological function.